触发人体免疫反应的新信号

StephenW

触发人体免疫反应的新信号

日期：
    2022 年 9 月 15 日
资源：
    克利夫兰诊所
概括：
    研究人员发现，被称为肌动蛋白细胞骨架的细胞结构的破坏是身体对病毒作出反应的“启动信号”。这些发现可能为开发新的抗病毒疫苗和治疗方法奠定基础。
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完整的故事

克利夫兰诊所佛罗里达研究与创新中心 (FRIC) 的研究人员发现，被称为肌动蛋白细胞骨架的细胞结构的破坏是身体对病毒作出反应的“启动信号”。本周发表在《细胞》杂志上的这些发现可能为开发新的抗病毒疫苗和治疗方法奠定了基础。

以前，病毒遗传物质（如 RNA）被认为是细胞中某些传感器分子触发免疫反应的唯一要求——这是许多类型细胞的“警报系统”。 RNA 还通过训练患者的免疫系统识别病毒作为疫苗的基础。这项新研究表明，信号传导过程还需要破坏细胞内的肌动蛋白细胞骨架，当病毒感染细胞时就会发生这种情况。

“这是考虑如何激活免疫系统的一种基本的新方法，其含义是这可能导致广泛的抗病毒治疗，”亚瑟和玛丽林莱维特基金会主席兼科学主任 Michaela Gack 博士说FRIC。 “我们的数据显示，这个过程在不同类型的 RNA 病毒中很常见。”

由蛋白质肌动蛋白组成的细胞骨架可作为细胞的结构支撑，但也是细胞生长、分裂和内化关键物质能力等过程的关键。 Gack 博士说，病毒会扰乱细胞骨架，但疫苗成分和某些疗法也会扰乱细胞骨架。

“我们的细胞免疫监视系统是否能感知到这一过程并引发抗病毒反应，目前尚不清楚，”Gack 博士说。 “我们的工作表明，特定的免疫受体感知病毒诱导的肌动蛋白细胞骨架重排，然后触发警报。”

尽管已经存在了几十年，但在 COVID-19 大流行期间，人们对使用 RNA 作为疫苗和疗法的基础的兴趣呈指数级增长。研究表明，多种病毒的触发系统是相似的，包括寨卡病毒、流感病毒或导致 COVID-19 的病毒 SARS-CoV-2。

Gack 博士的团队，包括主要作者、FRIC 的研究助理 Dhiraj Acharya 博士，还发现脂质成分或病毒样颗粒（例如用于疫苗或基于 RNA 的疗法中的那些颗粒）可能会导致提示所需的细胞骨架紊乱。一种免疫反应。这些结果可以帮助开发人员“微调”治疗剂或疫苗的免疫刺激效力。

Gack 博士的实验室在克利夫兰诊所的多地点全球病原体和人类健康研究中心下运作，在分子水平上研究病毒与宿主的相互作用，确定可在开发新疗法和疫苗中发挥关键作用的宿主反应。该中心是克利夫兰创新区的基石。

该研究是与德国乌尔姆大学 Konstantin Sparr 博士和来自多个机构的其他合作者合作开展的。资金由美国国立卫生研究院、德国联邦教育与研究部和德国研究基金会提供。

故事来源：

材料由克利夫兰诊所提供。注意：内容可能会根据样式和长度进行编辑。

StephenW

New signal for triggering human immune response

Date:
    September 15, 2022
Source:
    Cleveland Clinic
Summary:
    Researchers found that disruption of a cellular structure, known as the actin cytoskeleton, is a 'priming signal' for the body to respond to a virus. These findings potentially lay the groundwork for development of new anti-viral vaccines and treatments.
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FULL STORY

Researchers from Cleveland Clinic's Florida Research and Innovation Center (FRIC) found that disruption of a cellular structure, known as the actin cytoskeleton, is a "priming signal" for the body to respond to a virus. These findings, published in Cell this week, potentially lay the groundwork for development of new anti-viral vaccines and treatments.

Previously, viral genetic material such as RNA was considered the sole requirement for certain sensor molecules that live in cells to trigger an immune response -- an "alarm system" for many types of cells. RNA also serves as a basis for vaccines through training a patient's immune system to recognize a virus. This new study showed that the signaling process also requires disrupting the actin cytoskeleton inside cells, which occurs when a virus infects cells.

"It's a fundamental new way of considering how the immune system can be activated, and the implications are that this could lead to broad antiviral therapeutics," says Michaela Gack, Ph.D.,the Arthur and Marylin Levitt Endowed Chair and Scientific Director of the FRIC. "Our data shows this process is common across different types of RNA viruses."

Cytoskeletons, made up of the protein actin, serve as structural support for cells but are also key in processes like the cell's ability to grow, divide and internalize key substances. A virus disturbs the cytoskeleton, but so can vaccine components and certain therapeutics, Dr. Gack says.

"Whether this process is sensed by our cellular immune surveillance system and can trigger an antiviral response has been unknown," says Dr. Gack. "Our work showed that specific immune receptors sense actin cytoskeleton rearrangements induced by viruses and then trigger alarm."

Despite being around for decades, interest in using RNA as the basis for vaccines and therapeutics grew exponentially during the COVID-19 pandemic. The research showed that the triggering system is similar across multiple viruses, including Zika, the flu or SARS-CoV-2, the virus that causes COVID-19.

Dr. Gack's team, including lead author Dhiraj Acharya, Ph.D., research associate at FRIC, also discovered that lipid components or virus-like particles such as those used in vaccines or RNA-based therapeutics can cause the cytoskeletal disturbance necessary for prompting an immune response. These results could help developers "fine-tune" the immunostimulatory potencies of therapeutics or vaccines.

Dr. Gack's lab, operating under Cleveland Clinic's multi-site Global Center for Pathogen and Human Health Research, investigates virus-host interactions on a molecular level, identifying host responses that can play a key role in developing new treatments and vaccines. The center is a cornerstone of the Cleveland Innovation District.

The study was a collaboration with Konstantin Sparrer, Ph.D., Ulm University in Germany, and other collaborators from multiple institutions. Funding was provided by the National Institutes of Health, the Federal Ministry of Education and Research Germany, and the German Research Foundation.

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Materials provided by Cleveland Clinic. Note: Content may be edited for style and length.